The Center for Biomolecular Structure and Dynamics (CBSD) at the University of Montana (UM) is rooted in structural biology but multidisciplinary in scope. The rationale that underlies this program is based on the perception that effective biomedical innovation is driven from an understanding of macromolecular structure, which in turn, must be grounded on principles of experimental and theoretical chemistry. CBSD faculty are drawn from Department of Chemistry & Biochemistry, the Division of Biological Science and the Department of Biomedical and Pharmaceutical Sciences. Among this group are CBSD faculty with expertise in spectroscopy, structural biology, biochemistry and mechanistic and theoretical chemistry. We build on a strong foundation of sustained institutional support. Associated with the CBSD is a newly established interdisciplinary graduate program in Biochemistry and Biophysics. The goal of the proposed COBRE is to integrate investigators with research interests in cell and molecular physiology, mechanistic biochemistry, chemical biology, and theoretical and computational chemistry, into an interactive and collaborative network. With the creation of a CBSD COBRE, it is our goal to give structure to this vision by implementing the four aims of this proposal: Aim 1. Provide research support for five interdisciplinary research projects within the COBRE theme. These projects use theoretical and physical chemical methods to elucidate the catalytic mechanisms of enzymes involved in signal transduction and tryptophan catabolism. Structure-based homology modeling and chemical biology approaches will be used to design new ligands for the opioid receptor and to characterize the binding sites of the multidrug resistance transporter. Heteronuclear NMR experiments will be used to elucidate the structures of critical domains in the Junin arenavirus membrane fusion glycoprotein. Aim 2 shall be to recruit two new faculty members to CBSD-affiliated departments to build on existing strengths and introduce new expertise within the CBSD. Aim 3 will support collaborative activities involving CBSD faculty by sustaining of critical core research facilities in Macromolecular X-ray diffraction, Macromolecular NMR, BioSpectroscopy and Molecular Computation. Aim 4 will establish a supportive program to sustain an intellectually vibrant and cohesive CBSD that promotes infrastructure development, mentoring, scientific exchange and collaboration, with a robust advisory and self-assessment structure.